PT  - JOURNAL ARTICLE
AU  - Jesus Bertran-Gonzalez
AU  - Caroline Dinale
AU  - Miriam Matamales
TI  - Restoring functional D2- to D1-neuron correspondence enables goal-directed action control in long-lived striatal circuits
AID  - 10.1101/2022.09.14.508004
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.09.14.508004
4099  - http://biorxiv.org/content/early/2022/09/15/2022.09.14.508004.short
4100  - http://biorxiv.org/content/early/2022/09/15/2022.09.14.508004.full
AB  - Multidisciplinary evidence suggests that instrumental performance is governed by two major forms of behavioural control: goal-directed and autonomous processes. Brain-state abnormalities affecting the striatum, such as ageing, often shift control towards autonomous—habit-like—behaviour, although the neural mechanisms responsible for this shift remain unknown. Here, combining instrumental conditioning with cell-specific functional mapping and manipulation in striatal neurons, we explored strategies that invigorate goal-directed action capacity in aged mice. In animals performing instrumental actions, D2- and D1-neurons of the aged striatum were engaged in a characteristically counterbalanced manner, something that related to the propensity to express autonomous behaviour. Long-lasting, cell-specific desensitisation of D2-neurons in aged transgenic mice recapitulated the uneven D2- to D1-neuron functional correspondence observed in young mice, an effect that enabled successful goal-directed action. Our findings contribute to the understanding of the neural bases of behavioural control and propose neural system interventions that enhance cognitive functioning in habit-prone brains.Competing Interest StatementThe authors have declared no competing interest.